KIR3DL2 Binds to HLA-B27 Dimers and Free H Chains More Strongly than Other HLA Class I and Promotes the Expansion of T Cells in Ankylosing Spondylitis
| العنوان: | KIR3DL2 Binds to HLA-B27 Dimers and Free H Chains More Strongly than Other HLA Class I and Promotes the Expansion of T Cells in Ankylosing Spondylitis |
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| المؤلفون: | A Ridley, Isabel Wong-Baeza, Simon Brackenbridge, Jackie Shaw, Christopher Piper, Oliwia Rysnik, Hiroko Hatano, Anthoni Chan, Ricardo A. Fernandes, Kirsty McHugh, Paul Bowness, Simon Kollnberger |
| المصدر: | Journal of Immunology. 190(7) |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | musculoskeletal diseases, Cell Survival, T cell, Immunology, Plasma protein binding, Human leukocyte antigen, HLA-A3 Antigen, Biology, Article, Cell Line, HLA-B7 Antigen, Interferon-gamma, T-Lymphocyte Subsets, medicine, Humans, Immunology and Allergy, Spondylitis, Ankylosing, cardiovascular diseases, Antigens, Receptor, skin and connective tissue diseases, Cells, Cultured, HLA-B27 Antigen, Histocompatibility Antigens Class I, Receptors, KIR3DL2, Transfection, Ligand (biochemistry), Virology, Molecular biology, Killer Cells, Natural, medicine.anatomical_structure, KIR3DL2, Cell culture, HLA-B35 Antigen, Protein Multimerization, Protein Binding |
| الوصف: | The human leukocyte Ag HLA-B27 (B27) is strongly associated with the spondyloarthritides. B27 can be expressed at the cell surface of APC as both classical β2-microglobulin–associated B27 and B27 free H chain forms (FHC), including disulfide-bonded H chain homodimers (termed B272). B27 FHC forms, but not classical B27, bind to KIR3DL2. HLA-A3, which is not associated with spondyloarthritis (SpA), is also a ligand for KIR3DL2. In this study, we show that B272 and B27 FHC bind more strongly to KIR3DL2 than other HLA-class I, including HLA-A3. B272 tetramers bound KIR3DL2-transfected cells more strongly than HLA-A3. KIR3DL2Fc bound to HLA-B27–transfected cells more strongly than to cells transfected with other HLA-class I. KIR3DL2Fc pulled down multimeric, dimeric, and monomeric FHC from HLA-B27–expressing cell lines. Binding to B272 and B27 FHC stimulated greater KIR3DL2 phosphorylation than HLA-A3. B272 and B27 FHC stimulated KIR3DL2CD3ε-transduced T cell IL-2 production to a greater extent than control HLA-class I. KIR3DL2 binding to B27 inhibited NK IFN-γ secretion and promoted greater survival of KIR3DL2+ CD4 T and NK cells than binding to other HLA-class I. KIR3DL2+ T cells from B27+ SpA patients proliferated more in response to Ag presented by syngeneic APC than the same T cell subset from healthy and disease controls. Our results suggest that expansion of KIR3DL2-expressing leukocytes observed in B27+ SpA may be explained by the stronger interaction of KIR3DL2 with B27 FHC. |
| اللغة: | English |
| تدمد: | 1550-6606 0022-1767 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4a5761d6b96c607893c8a0a0a9223862Test http://ora.ox.ac.uk/objects/uuid:89ed8d73-9065-4e8b-96a8-1c19037b94f9Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4a5761d6b96c607893c8a0a0a9223862 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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